Testing the hypothesis, that targeted biopsy is a better way to detect potentially lethal prostate cancer than conventional blind biopsy, is a major unmet need and the subject of this proposal. One million prostate biopsies are performed annually in the U.S. An estimated 99% of the biopsy procedures employ a method little changed since the 1980s. That 30-year old ultrasound-guided biopsy method does not usually allow tumor- targeting, and thus results in the serious dual problem of over-detection of insignificant cancers and under- detection of potentially lethal cancers. We and others have found that targeted prostate biopsy appears to help rectify both problems, but all reports to date are essentially pilot studies or comparisons which are underpowered or lack adequate controls. We aim to test that hypothesis in a Phase II clinical trial, which would allow direct comparison of conventional ultrasound-guided biopsy with two forms of targeted biopsy. Biopsy nave men suspected of prostate cancer (T1c) would undergo a multiparametric MRI (mpMRI) prior to biopsy. Each patient with a suspicious MR finding (PI-RADS >3) would then serve as his own control, undergoing three types of biopsy: first an ultrasound- guided systematic sampling, then visual targeting (cognitive) under radiologic direction, then MRI-ultrasound fusion targeting using the Artemis device. Primary outcome is detection of cancers of Gleason Score >7, measured in mm of cancer involvement in individual biopsy cores. The trial employs power estimates based on extensive in-house data from targeted biopsy procedures performed over the past 5 years at UCLA. No such trial, which has been adequately powered and controlled, has yet been performed. Comparing the two methods of targeting, a secondary aim in the trial, is important, since cognitive biopsy is less expensive and somewhat quicker than device-fusion biopsy. However, cognitive biopsy does not permit biopsy site tracking, as does device-fusion biopsy, and appears less precise. Therefore, establishing the relative value of the two methods has great practical importance, both clinically and economically. The value of Restriction Spectrum Imaging (RSI), an analytic supplement to diffusion-weighted imaging, will also be studied. RSI has been used extensively to diagnose brain tumors and has recently been shown to add sensitivity and specificity to prostate cancer detection in MRI-prostatectomy correlations. We aim to further the early studies of RSI with an initial exploration of this innovation in men undergoing prostate biopsy. We anticipate that targeted biopsy will show a higher detection rate of Gleason >7 cancers than conventional biopsy. If true, the basis for a major change in the path to prostate cancer diagnosis, treatment, and active surveillance follow-up could be established. Prostate biopsy would become more rational than it is today, and fewer procedures would be required to reach a correct diagnosis. If the hypothesis is confirmed, the value of the new method would gain Level 1 evidence, and the basis for a definitive Phase III trial would be established.